1. Field of the Invention
This invention is directed to polymeric matrices designed for controlled release of biologically active substances, such as therapeutic bacteriophage which can kill bacteria capable of causing disease.
2. Review of Related Art
Bioactive composites based on biodegradable (or more precisely, bioerodible) polymers as matrices, impregnated by bactericidal substances are promising for the treatment of superficial infected wounds. On the one hand, bactericidal substances clean the wound from bacteria and make favorable conditions for wound healing, and prevent bacterial invasion through the holes made in wound coverings for exudate drainage, on  drainage. On the other hand, biodegradable polymer which is able to timely release enough degradation products (polymeric debris) can activate macrophages to produce the required growth factors acrd and, in that way, can accelerate wound healing (Pratt, et al. (1994, “Dimehtyltitanocene-Induced Surface Chemical Degradation of Synthetic Bioabsorbable Polyesters”, J. Polym. Sci. Part 0.4: Polym. Chem., 32(5):949; Greisler, (1988), “Small Diameter Vascular Prostheses: Macrophage-Biomaterial Interactions with Bioresorbable Vascular Prostheses”. Transactions of ASAIO, 34:1051).
Mori, et al., U.S. Pat. No. 3,867, 520, discloses a delivery system for therapeutic agents using films made of polyamino acid polymers with oil-like or wax-like substances dispersed in the film. Therapeutic agents are dissolved in the carrier, and when the film is applied to an internal or external surface of the body, the carrier migrates to the surface of the film where the agent is released. However, these films are not biodegraded during use.
Sidman, U.S. Pat. No. 4,351,337, discloses an implantable delivery device comprising a matrix formed of a poly-alpha-amino acid component having one or more drugs and/or diagnostic agents physically contained therein. The drug or diagnostic agent is released through diffusion and/or biodegradation resulting from the action on the polymeric matrix of enzymes present in the host into which the implant is placed.
Taniharak, et al., U.S. Pat. No. 5,770,229, discloses a medical polymer gel made up of a cross-linked polysaccharide with a drug attacked  attached to the polysaccharide via a linkage that is cleavable by an endogenous enzyme. This system provides for delayed release of the attached drug from the polymer, but the release rate is subject to individual variation in the amount of the endogenous enzyme, and the polymer, while biocompatible, is not biodegradable.
Kuroyangi and coworkers (1992, J. Appl. Biomater., 3:153-161) have developed a wound dressing for burn care that is a hydrophobic poly-L-leucine spongy matrix impregnated with antibacterial silver sulfadiazine supported by a fine nylon mesh. This wound dressing suppresses bacterial growth while controlling fluid loss. However, the dressing is not degraded, but rather sticks to the wound until it separates spontaneously from the healed skin.
Georgian Patent No. 1090 describes a wound dressing containing 45-50 wt. % biodegradable poly(ester-amide) based on natural alpha-amino acids impregnated with 50-55 wt. % dried bacteriophage. The poly(ester-amide) is not characterized in detail, but the dressing also has 0.05-0.15 wt. % surface immobilized alpha-chymotrypsin. The impregnated poly(ester-amide) is formed into a film, and the film is used to accelerate healing of superficial wounds, including burns.
Tsitlanadze, et al., in an abstract from Int. Symp. Biodegrad. Mater, Oct. 7-9, 1996, Hamburg, Germany, describe alpha-chymotrypsin-catalyzed hydrolysis of regular poly (ester-amides) (PEAs) of general formula I: where                k=2, 3, 4, or 6        m=4 or 8, and        R=CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, (CH2)3CH3, CH2C6H5, or (CH2)3SCH3.        
It is reported that alpha-chymotrypsin is spontaneously immobilized on the surface of the PEAs from aqueous solution, and erodes the polymer surface under physiologic conditions, with increasing lysis for more hydrophobic R groups and more hydrophobic polymer backbone. A biocomposite material based on a PEA polymer containing bacteriophages, antibiotic or anesthetic was prepared for study as artificial skin for healing burns and festering wounds.